Table 3 Investigations of structure and function of heart and / or arteries in children and adolescents with JIA with no clinical signs of cardiovascular dysfunction

Stamato et al. 1995 [78]

Descriptive cross-sectional

36

36 HLA-B27 pos. with spondylarthropathy

No information

Echocardiographic assessment of left ventricle and the outflow tract.

Mild aortal regurgitation in patients unrelated to disease duration

with an age matched healthy control group

33 ^*

Atrio-ventricular conduction

Disease duration

Huppertz et al. 2000 [79]

Descriptive cross- sectional

40

35 HLA-B27 pos ERA

No information

Echocardiographic assessment of the left ventricle functions before and after exercise.

HLA-B27 positive ERA possibly at risk for development of aortic regurgitation and impaired myocardial relaxation

with a control group of age and sexmatched HLA-B27 neg JIA and 25 healthy children

15 + 25 ^*

3 oligo

Atrio-ventricular conduction

1 sJIA

BP

1 unclassified

Oguz et al. 2000 [80]

Descriptive cross- sectional.

30

19 oligo

Mainly NSAID

Echocardiographic assessment of the left ventricle function

Higher systolic and diastolic BP, but within normal limits, and diastolic dysfunction of abnormal relaxation type in patients

with an age matched healthy control group

30 ^*

10 poly

The patient with systemic JIA received corticosteroid

BP

1 sJIA.

One unspecified patient received MTX

Argyropoulou et al. 2003 [81]

Descriptive cross-sectional

31

18 oligo

No information

Evaluation by MR of aortic distensibility and PWV

Lower distensibility and higher PWV in patients unrelated to JIA subtype

with an age matched healthy control group

28 ^*

6 poly

Disease activity

No correlations between aortic distensibility / PWV and metabolic and disease activity parameters

Insulin sensitivity

Lipid profile

7 sJIA

Bharti et al. 2004 [82]

Descriptive cross-sectional.

35

oligo

All received NSAID

Eccocardiographic evaluation of left ventricular function

Higher systolic and diastolic BP, but within normal rate, and higher resting heart rate in patients.

with an age matched healthy control group

35 ^*

poly

Diastolic dysfunction and higher systolic and diastolic dimensions and volumes.

sJIA

No numbers given

Pietrewicz et al. 2007 [83]

Descriptive cross-sectional

40

32 oligo

No information

Echocardiographic assessment of cIMT

Increased cIMT in patients with JIA, highest in children with polyarthritis, and correlation between homocystein and cIMT

Homocysteine

with an age matched control group of healthy children

23 ^*

8 poly

CRP

Lipid profile

Correlation between disease duration and cIMT

Disease duration

Vlahos et al. 2011 [84]

Descriptive cross-sectional

30

15 oligo

3 NSAID

Echocardiographic assessment of cIMT

Reduced FMD in patients (as a group) associated with ESR but without any association to medication or clinical disease activity

with a BMI, sex, and age matched control group of healthy children

33 ^*

8 poly

4 corticosteroid

PWV

FMD

7 sJIA

15 MTX

Arterial compliance

Increased cIMT in sJIA compared to controls or non-systemic JIA and related to use of corticosteroids, disease activity, BMI, blood pressure, dyslipidaemia, and age

9 TNF-inhibitor

Disease activity

BMI

BP

Glucose

Lipid profile

No difference in PWV or arterial compliance between groups

Smoking

Koca et al. 2012 [85]

Descriptive cross-sectional

50

22 oligo

No information

Echocardiographic assessment of left ventricle function

Impaired diastolic function in patients

13 poly

Electrographic assessment

No arrhythmias

6 ERA

4 PsA

5 sJIA

with a sex, and age matched control group of healthy children

70 ^*

Follow-up after 12 month.

Abul et al. 2012 [86]

Descriptive cross-sectional

55

24 oligo

22 NSAID

Echocardiographic assessment of right ventricular function

Systolic and diastolic dysfunction of the right ventricle

8 poly

31 Salazopyrin

15 ERA

31 MTX

with a BMI, sex, and age matched control group of healthy children

33 ^*

1 PsA

25 Corticosteroid

Disease activity

No association to medication including steroids and no associations to disease activity

7 sJIA

2 TNF-inhibitor

Alkady et al. 2012 [66]

Descriptive cross- sectional

45

5 oligo

NSAID

Echocardiographic assessment of systolic and diastolic function (36 patients)

Higher resting heart rate and higher systolic and diastolic BP in patients but within normal range. Also enlarged left ventricular systolic dimensions and diastolic dysfunction. In 6 patients was found thickened pericardium, and in 9 mitral valve thickening and mild dysfunction.No association with disease activity reported.

10 poly

26 MTX

20 ERA

8 Corticosteroid

with a sex and age matched control group of healthy children

30 ^*

1 PsA

Spirometry and CO diffusion (30 patients)

9 sJIA

23 patients and controls had both investigations

Disease activity and duration

In 19 out of 30 patients was found a reduction in pulmonary function primarily of a restrictive pattern, inversely correlated to disease duration and severity / treatment with MTX

Breda et al. 2012 and 2013 [33, 34]

Longitudinal intervention study of 12 months

38

Oligo- or poly

NSAID

cIMT

Improvement in all baseline disease parameters, including BT, after one year of “ treatment to target” except cHDL that was found normal at baseline and did not change. Positive correlation between cIMT and LDL and IL-1beta, no correlation to CRP or ESR.

BT was found elevated at baseline but within normal range

Mild disease in 22

MTX at baseline.

Clinical disease activity

ESR, CRP

with a sex, age and puberty stage matched control group of healthy children

40 ^*

Aggressive disease in 16 with poly

During follow-up disease control was obtained by 22 in treatment with NSAID +/- conventional DMARDs

Proinflammatory cytokines

BP

Lipid profile

Oxidant status

16 patients needed more aggressive treatment with TNF-alfa inhibition

Glowinska-Olszewska et al. 2013 [32]

Descriptive cross- sectional

58

28 oligo

42 Corticosteroid

BMI

22% of the patients met the criteria for overweight or obesity.

26 poly

28 MTX

FMD

4 sJIA

14 Biologics

cIMT

Clin. active inflammation: 30

9 Unspec. DMARDS

LVMi

Lower FMD and higher cIMT, LVMi, BMI, and BP in patients as a group compared to controls; highest cIMT and lowest FMD in obese patients. No difference between patients with clinically active and inactive disease and no difference between JIA subtypes.

Disease activity

BP

CRP

IL-6, TNF-alfa

Lipid profile

Insulin sensitivity

with a sex and age matched control group of healthy children with normal weight; no obese children

36 ^*

Clin. inactive inflammation: 28

Raab et al. 2013 [36]

Descriptive cross- sectional study of young adults with severe JIA, based on self-reports

344

28 oligo

215 Biologics

Comorbidity

In 9.9% were reported CVD with hypertension in 7.3%, not different from the control group

50 extended oligo

91 RFneg poly

37 RFpos poly

151 MTX

Disease activity

75 ERA

64 Other conventional

Health

CVD, mainly hypertension, was reported in 40.6% of 15 patients with sJIA

37 PsA

DMARDs

Functional deficits,

15 sJIA

11 other arthritis

and compared to an age and sex matched cohort sampled from the general population

688 ^*

Aulie et al. 2014 [37]

Cross-sectional, observational study of patients with disease duration of more than 23 years

87

15 oligo

25 TNF-inhibitor

BP

Higher systolic and diastolic BT and small elevation of PWV in patients related to diastolic BT

14 extended oligo

19 Methotrexate

PWV

13 RF neg poly

23 Daily NSAID

AIx

5 RF pos poly

6 Prednisolone

Coronary calcification

18 ERA

Disease activity

No difference in AIx between patients and controls, but a positive association to diastolic BP, accumulated disease parameters inclusive treatment with prednisolone, and daily smoking, and a negative association to vigorous physical activity

15 PsA

CRP, ESR

BMI and waist circumference

4 sJIA

Lipid profile

3 unclassified

Insulin resistance

Self reported habits of smoking and physical activity

With an age and sex matched group without DM or inflammatory arthritis selected from a national population register

87 ^*

Coronary calcification was present in 26% of patients, a frequency not different from that found in a large population study, and related to waist circumference, BMI, systolic BP, blood glucose and years on daily prednisolone

Lianza et al. 2014 [77]

Two year prospective observational study

21

21 poly

TNF-inhibitor

Systolic and diastolic cardiac function evaluated by echocardiography

Mild ventricular diastolic dysfunction in JIA with no relation to NT-pro-BNP. Possible association between NT-pro-BNP and disease activity.

with age and sex matched healthy controls

22 ^*

Cardiac biomarkers: NT-pro-BNP

Troponin T

No sign of cardiovascular deterioration during treatment with TNF-alfa inhibitor.

Disease activity

Satija et al. 2014 [71]

Cross sectional, observational

31

2 oligo

No DMARD or biologics

cIMT,

Reduced arterial elasticity in patients indicative of increased stiffness, all had normal BT. No difference in cIMT, FMD, GTN-MD between subgroups and controls

2 RF neg poly

Arterial elasticity

FMD

31 ^*

GTN-MD

BT

4 RF pos poly

Disease activity

9 ERA

ESR

14 sJIA

Lipid-profile

Correlation between cIMT and ESR

With an age and sex matched control group of healthy children